Stem cells from the dental apical papilla in extracellular matrix hydrogels mitigate inflammation of microglial cells

Abstract

After spinal cord injury (SCI) chronic inflammation hampers regeneration. Influencing the local microenvironment after SCI may provide a strategy to modulate inflammation and the immune response. The objectives of this work were to determine whether bone or spinal cord derived ECM hydrogels can deliver human mesenchymal stem cells from the apical papilla (SCAP) to reduce local inflammation and provide a regenerative microenvironment. Bone hydrogels (8 and 10 mg/ml, B8 and B10) and spinal cord hydrogels (8 mg/ml, S8) supplemented with fibrin possessed a gelation rate and a storage modulus compatible with spinal cord implantation. S8 and B8 impact on the expression of anti and pro-inflammatory cytokines (Arg1, Nos2, Tnf) in LPS treated microglial cells were assessed using solubilised and solid hydrogel forms. S8 significantly reduced the Nos2/Arg1 ratio and solubilised B8 significantly reduced Tnf and increased Arg1 whereas solid S8 and B8 did not impact inflammation in microglial cells. SCAP incorporation within ECM hydrogels did not impact upon SCAP immunoregulatory properties, with significant downregulation of Nos2/Arg1 ratio observed for all SCAP embedded hydrogels. Tnf expression was reduced with SCAP embedded in B8, reflecting the gene expression observed with the innate hydrogel. Thus, ECM hydrogels are suitable vehicles to deliver SCAP due to their physical properties, preservation of SCAP viability and immunomodulatory capacity.

High concentrations of calcium suppress osteogenic differentiation of human periodontal ligament stem cells in vitro

“…Dental mesenchymal stem cells, which are multipotent stem cells found in the mouth that are used to treat inflammatory diseases or regenerate periodontium, are currently in the spotlight. 27 , 28 Elucidating the relationship between the changes in the oral cavity environment and the process of hPDLSC differentiation will aid in improving periodontium regeneration and preventing periodontitis. Although there are various restrictions on the clinical applications of stem cell differentiation, our finding may be a good approach for future clinical applications in periodontal tissue regeneration.…”

Dental Stem Cell Banking and Applications of Dental Stem Cells for Regenerative Medicine

“…They call for future research to be conducted regarding the immunogenicity of the cells and suggest that SCAP may be an ideal candidate for stem cell banking [15]. Current research focuses on identifying the precise biomaterials that make up the environment in which SCAP best contributes to tissue regeneration such as oxygen level [43] and ideal makeup of a transplant carrier [44,45].…”

Potential Applications of Advanced Nano/Hydrogels in Biomedicine: Static, Dynamic, Multi‐Stage, and Bioinspired

“…These hydrogels were based on ECM derived from the spinal cord or bone and reduced inflammation, and at the same time enhanced regeneration of the spinal cord. [ 152 ] Bone marrow mesenchymal stem cells (BMSCs) also reduce chronic inflammation in the microenvironment of wounds, particularly in diabetic ulcers. Chen et.…”